Anterior cruciate ligament (ACL) injuries can cause serious disability and degeneration of the knee joint. Primary repair is not efficacious and currently available grafts or prostheses are not ideally suited for ACL reconstruction. Tissue engineering, an emerging technology combining resorbable scaffolds, cells, and modulators of cell behavior, may revolutionize treatment of musculoskeletal soft tissue injuries by providing alternatives to biological grafts and permanent synthetic prostheses. The three specific aims of this study are to understand and improve neoligament formation by utilizing tissue engineering strategies: Aim number 1: Test the hypothesis that the quality of the neoligament tissue is directly related to the strength retention profile of the scaffold, by comparing the efficacy of 3 types of resorbable scaffolds with similar biocompatibility but different strength retention: collagen scaffolds (rapid strength loss), polyarylate scaffolds (intermediate strength loss), and polycarbonate scaffolds (prolonged strength retention). Aim number 2: Test the hypothesis that neoligament formation is accelerated by pre-seeding the scaffold with fibroblasts, by comparing the relative efficacy of unseeded scaffolds vs. 'ligament analogs' pre-seeded in vitro with skin or ACL fibroblasts. These fibroblasts are known to have different healing potentials. Aim number 3: Test the hypothesis that neoligament formation is enhanced by modulating the behavior of local repair cells, by incorporating specific polypeptide growth factors (known to influence normal tissue repair) into the ACL reconstruction scaffolds. Completion of these studies in a well-established animal model will lead to a better understanding of the mechanisms of neoligament formation in response to resorbable scaffolds, seeded cells, and modulators of cell behavior. This knowledge may provide a 'blueprint' for development of a novel approach for reconstruction of the ACL and other non-healing musculoskeletal soft tissues.